Although an older drug, fluoropyrimidines continue to be an integral component of chemotherapy for a number of cancers, including such common ones as breast and colon cancer. Our knowledge about the complex metabolism of fluoropyrimidines has increased exponentially and we now know that a small percentage of patients do not clear them well and are subjected to severe toxicity. Current research suggests that nearly 8% of the population has at least a partial DPD deficiency. A diagnostic determination test for DPD deficiency is available and it is expected that with a potential 500,000 people in North America using 5-FU this form of testing will increase. It is generally accepted that these tests can serve to diagnose DPD deficiency in patients with greater than expected fluoropyrimidine toxicty; however, prospective studies of the strategy of universal testing of all FU candidates needs to be subjected to prospective randomized trials and is not currently recommended.
van Kuilenburg, Andre B. P., Meinsma, Rutger, Zonnenberg, Bernard A., Zoetekouw, Lida, Baas, Frank, Matsuda, Koichi, Tamaki, Nanaya, van Gennip, Albert H. Dihydropyrimidinase Deficiency and Severe 5-Fluorouracil Toxicity
Clin Cancer Res 2003 9: 4363-4367
H. H. Ezzeldin and R. B. Diasio Predicting Fluorouracil Toxicity: Can We Finally Do It? J. Clin. Oncol., May 1, 2008; 26(13): 2080 – 2082.
Role of Genetic and Nongenetic Factors for Fluorouracil Treatment-Related Severe Toxicity: A Prospective Clinical Trial by the German 5-FU Toxicity Study Group Matthias Schwab, Ulrich M. Zanger, Claudia Marx, Elke Schaeffeler, Kathrin Klein, Jürgen Dippon, Reinhold Kerb, Julia Blievernicht, Joachim Fischer, Ute Hofmann, Carsten Bokemeyer, and Michel Eichelbaum JCO 2008 26: 2131-2138